The incidence of type 2 diabetes in youth could rise by nearly 700% by 2060 if recent trends for the disease continue, according to a new study published in Diabetes Care.

It is expected that as many as 526,000 people younger than 20 years in the United States will have diabetes by 2060, researchers from the Centers for Disease Control and Prevention report. Their projections found that the number of young people with diabetes will increase 12%, from 213,000 in 2017 to 239,000 in 2060.

The estimates include a 673% rise in the number of youth with type 2 diabetes and a 65% increase in cases of type 1 diabetes over the next 4 decades.

Most of the new cases are projected to occur among non-Hispanic Blacks, exacerbating the already significant racial disparities in type 2 diabetes in particular, the study found.

“This study’s startling projections of type 2 diabetes increases show why it is crucial to advance health equity and reduce the widespread disparities that already take a toll on people’s health,” Christopher Holliday, PhD, MPH, FACHE, director of CDC’s Division of Diabetes Translation, said in a press release about the new estimates.

Even if trends remain the same in coming decades, researchers said diagnoses of type 2 diabetes will rise almost 70% and that diagnoses of type 1 diabetes will increase by 3%.

The researchers attribute the increase in diabetes cases among youth to a variety of factors, including the growing prevalence of childhood obesity and the presence of diabetes in women of childbearing age, which is linked to obesity in their offspring.

Debra Houry, MD, MPH, acting principal director of the CDC, said the focus should be on prevention.

“This new research should serve as a wake-up call for all of us. It’s vital that we focus our efforts to ensure all Americans, especially our young people, are the healthiest they can be,” she said in a press release.

The findings come from the SEARCH for Diabetes in Youth study, funded by the CDC and the National Institutes of Health. Dr. Houry and Dr. Holliday report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of type 2 diabetes in youth could rise by nearly 700% by 2060 if recent trends for the disease continue, according to a new study published in Diabetes Care.

It is expected that as many as 526,000 people younger than 20 years in the United States will have diabetes by 2060, researchers from the Centers for Disease Control and Prevention report. Their projections found that the number of young people with diabetes will increase 12%, from 213,000 in 2017 to 239,000 in 2060.

The estimates include a 673% rise in the number of youth with type 2 diabetes and a 65% increase in cases of type 1 diabetes over the next 4 decades.

Most of the new cases are projected to occur among non-Hispanic Blacks, exacerbating the already significant racial disparities in type 2 diabetes in particular, the study found.

“This study’s startling projections of type 2 diabetes increases show why it is crucial to advance health equity and reduce the widespread disparities that already take a toll on people’s health,” Christopher Holliday, PhD, MPH, FACHE, director of CDC’s Division of Diabetes Translation, said in a press release about the new estimates.

Even if trends remain the same in coming decades, researchers said diagnoses of type 2 diabetes will rise almost 70% and that diagnoses of type 1 diabetes will increase by 3%.

The researchers attribute the increase in diabetes cases among youth to a variety of factors, including the growing prevalence of childhood obesity and the presence of diabetes in women of childbearing age, which is linked to obesity in their offspring.

Debra Houry, MD, MPH, acting principal director of the CDC, said the focus should be on prevention.

“This new research should serve as a wake-up call for all of us. It’s vital that we focus our efforts to ensure all Americans, especially our young people, are the healthiest they can be,” she said in a press release.

The findings come from the SEARCH for Diabetes in Youth study, funded by the CDC and the National Institutes of Health. Dr. Houry and Dr. Holliday report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of type 2 diabetes in youth could rise by nearly 700% by 2060 if recent trends for the disease continue, according to a new study published in Diabetes Care.

It is expected that as many as 526,000 people younger than 20 years in the United States will have diabetes by 2060, researchers from the Centers for Disease Control and Prevention report. Their projections found that the number of young people with diabetes will increase 12%, from 213,000 in 2017 to 239,000 in 2060.

The estimates include a 673% rise in the number of youth with type 2 diabetes and a 65% increase in cases of type 1 diabetes over the next 4 decades.

Most of the new cases are projected to occur among non-Hispanic Blacks, exacerbating the already significant racial disparities in type 2 diabetes in particular, the study found.

“This study’s startling projections of type 2 diabetes increases show why it is crucial to advance health equity and reduce the widespread disparities that already take a toll on people’s health,” Christopher Holliday, PhD, MPH, FACHE, director of CDC’s Division of Diabetes Translation, said in a press release about the new estimates.

Even if trends remain the same in coming decades, researchers said diagnoses of type 2 diabetes will rise almost 70% and that diagnoses of type 1 diabetes will increase by 3%.

The researchers attribute the increase in diabetes cases among youth to a variety of factors, including the growing prevalence of childhood obesity and the presence of diabetes in women of childbearing age, which is linked to obesity in their offspring.

Debra Houry, MD, MPH, acting principal director of the CDC, said the focus should be on prevention.

“This new research should serve as a wake-up call for all of us. It’s vital that we focus our efforts to ensure all Americans, especially our young people, are the healthiest they can be,” she said in a press release.

The findings come from the SEARCH for Diabetes in Youth study, funded by the CDC and the National Institutes of Health. Dr. Houry and Dr. Holliday report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking more steps per day is associated with a progressively lower risk of cardiovascular disease (CVD) among older adults – and the benefits accrue at well below the widely promoted threshold of 10,000 steps per day, new research shows.

Among adults aged 60 and older, those who took roughly 6,000 to 9,000 steps per day had a 40% to 50% lower risk of CVD, compared with peers logging just 2,000 steps per day.

“We hope this study will contribute evidence to future public health and clinical guidance on how many steps we need for health,” Amanda Paluch, PhD, with University of Massachusetts Amherst, told this news organization.

Getting in more steps per day can lower an individual’s risk for heart disease – but it’s not an “all or nothing” situation, Dr. Paluch said.

“The heart health benefits begin at lower than 10,000 steps per day. So, for the many adults that may find 10,000 steps a bit out of reach, it is important to promote that even small increases in steps can be beneficial for health,” Dr. Paluch said.

The study was published online in Circulation.
 

Attainable step goals

As part of the Steps for Health Collaborative, Dr. Paluch and colleagues examined the dose-response relationship between steps per day and CVD in a meta-analysis of eight prospective studies involving 20,152 adults (mean age 63, 52% women).

Steps were measured in each study using one of five different commercially available step-measuring devices. Adults aged 60 years and older took a median of 4,323 steps per day (interquartile range, 2,760-6,924), while younger adults walked a bit more (median 6,911 daily steps; IQR, 4,783-9,794).

During follow-up lasting an average of 6.2 years, a total of 1,523 CVD events were reported.

In the final adjusted model, for older adults, compared with those in quartile 1 who got the fewest steps per day (median 1,811), the risk of CVD was 20% lower in those in quartile 2, who got a median of 3,823 steps per day (hazard ratio, 0.80; 95% confidence interval, 0.69-0.93).

CVD risk was 38% lower in older adults in quartile 3 who got a median of 5,520 steps per day (HR, 0.62; 95% CI, 0.52-0.74) and 49% lower in those in quartile 4 who walked the most (a median of 9,259 steps per day; HR, 0.51; 95% CI, 0.41-0.63).

Restricting the analysis to individuals without known CVD at baseline showed similar results.

Among six studies that excluded adults with a history of CVD at baseline, compared with the lowest quartile, the HR for incident CVD events was 0.74 (95% CI, 0.60-0.91) in the second quartile, 0.60 (95% CI, 0.47-0.77) in the third quartile, and 0.55 (95% CI, 0.40-0.76) in the fourth quartile.

Despite the inverse association of steps with CVD in older adults, there was no association in younger adults. The researchers caution, however, that CVD is a disease of aging, and the follow-up period in these studies may not have been long enough to capture CVD incidence in younger adults.

Stepping rate (pace or cadence) was not associated with CVD risk beyond that of total steps per day. However, only four of the eight studies reported data on stepping rate, so this finding should be viewed as preliminary, Dr. Paluch and colleagues say.
 

Start small and go from there

Dr. Paluch said the take-home message from this study and numerous others is simple.

“Move more and sit less! Being physically active, by getting in your steps, is an important part of keeping your heart healthy,” she said in an interview.

For adults who are currently inactive, Dr. Paluch suggests finding small ways to get in a few more steps per day. “It does not need to be drastic changes. Consider a brief 5- to 10-minute walking break at lunch, taking the stairs, or playing a game of hide and seek with the grandchildren,” Dr. Paluch advised.

“For adults starting at 3,000 steps a day, set a goal of 4,000, and then 5,000. Each improvement can lead to better heart health,” Dr. Paluch said. “And for those who are already active, keep it up, as there are benefits with higher volumes of steps per day as well.”

Support for this research was provided by the Intergovernmental Personnel Act Agreement through the Centers for Disease Control and Prevention. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking more steps per day is associated with a progressively lower risk of cardiovascular disease (CVD) among older adults – and the benefits accrue at well below the widely promoted threshold of 10,000 steps per day, new research shows.

Among adults aged 60 and older, those who took roughly 6,000 to 9,000 steps per day had a 40% to 50% lower risk of CVD, compared with peers logging just 2,000 steps per day.

“We hope this study will contribute evidence to future public health and clinical guidance on how many steps we need for health,” Amanda Paluch, PhD, with University of Massachusetts Amherst, told this news organization.

Getting in more steps per day can lower an individual’s risk for heart disease – but it’s not an “all or nothing” situation, Dr. Paluch said.

“The heart health benefits begin at lower than 10,000 steps per day. So, for the many adults that may find 10,000 steps a bit out of reach, it is important to promote that even small increases in steps can be beneficial for health,” Dr. Paluch said.

The study was published online in Circulation.
 

Attainable step goals

As part of the Steps for Health Collaborative, Dr. Paluch and colleagues examined the dose-response relationship between steps per day and CVD in a meta-analysis of eight prospective studies involving 20,152 adults (mean age 63, 52% women).

Steps were measured in each study using one of five different commercially available step-measuring devices. Adults aged 60 years and older took a median of 4,323 steps per day (interquartile range, 2,760-6,924), while younger adults walked a bit more (median 6,911 daily steps; IQR, 4,783-9,794).

During follow-up lasting an average of 6.2 years, a total of 1,523 CVD events were reported.

In the final adjusted model, for older adults, compared with those in quartile 1 who got the fewest steps per day (median 1,811), the risk of CVD was 20% lower in those in quartile 2, who got a median of 3,823 steps per day (hazard ratio, 0.80; 95% confidence interval, 0.69-0.93).

CVD risk was 38% lower in older adults in quartile 3 who got a median of 5,520 steps per day (HR, 0.62; 95% CI, 0.52-0.74) and 49% lower in those in quartile 4 who walked the most (a median of 9,259 steps per day; HR, 0.51; 95% CI, 0.41-0.63).

Restricting the analysis to individuals without known CVD at baseline showed similar results.

Among six studies that excluded adults with a history of CVD at baseline, compared with the lowest quartile, the HR for incident CVD events was 0.74 (95% CI, 0.60-0.91) in the second quartile, 0.60 (95% CI, 0.47-0.77) in the third quartile, and 0.55 (95% CI, 0.40-0.76) in the fourth quartile.

Despite the inverse association of steps with CVD in older adults, there was no association in younger adults. The researchers caution, however, that CVD is a disease of aging, and the follow-up period in these studies may not have been long enough to capture CVD incidence in younger adults.

Stepping rate (pace or cadence) was not associated with CVD risk beyond that of total steps per day. However, only four of the eight studies reported data on stepping rate, so this finding should be viewed as preliminary, Dr. Paluch and colleagues say.
 

Start small and go from there

Dr. Paluch said the take-home message from this study and numerous others is simple.

“Move more and sit less! Being physically active, by getting in your steps, is an important part of keeping your heart healthy,” she said in an interview.

For adults who are currently inactive, Dr. Paluch suggests finding small ways to get in a few more steps per day. “It does not need to be drastic changes. Consider a brief 5- to 10-minute walking break at lunch, taking the stairs, or playing a game of hide and seek with the grandchildren,” Dr. Paluch advised.

“For adults starting at 3,000 steps a day, set a goal of 4,000, and then 5,000. Each improvement can lead to better heart health,” Dr. Paluch said. “And for those who are already active, keep it up, as there are benefits with higher volumes of steps per day as well.”

Support for this research was provided by the Intergovernmental Personnel Act Agreement through the Centers for Disease Control and Prevention. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking more steps per day is associated with a progressively lower risk of cardiovascular disease (CVD) among older adults – and the benefits accrue at well below the widely promoted threshold of 10,000 steps per day, new research shows.

Among adults aged 60 and older, those who took roughly 6,000 to 9,000 steps per day had a 40% to 50% lower risk of CVD, compared with peers logging just 2,000 steps per day.

“We hope this study will contribute evidence to future public health and clinical guidance on how many steps we need for health,” Amanda Paluch, PhD, with University of Massachusetts Amherst, told this news organization.

Getting in more steps per day can lower an individual’s risk for heart disease – but it’s not an “all or nothing” situation, Dr. Paluch said.

“The heart health benefits begin at lower than 10,000 steps per day. So, for the many adults that may find 10,000 steps a bit out of reach, it is important to promote that even small increases in steps can be beneficial for health,” Dr. Paluch said.

The study was published online in Circulation.
 

Attainable step goals

As part of the Steps for Health Collaborative, Dr. Paluch and colleagues examined the dose-response relationship between steps per day and CVD in a meta-analysis of eight prospective studies involving 20,152 adults (mean age 63, 52% women).

Steps were measured in each study using one of five different commercially available step-measuring devices. Adults aged 60 years and older took a median of 4,323 steps per day (interquartile range, 2,760-6,924), while younger adults walked a bit more (median 6,911 daily steps; IQR, 4,783-9,794).

During follow-up lasting an average of 6.2 years, a total of 1,523 CVD events were reported.

In the final adjusted model, for older adults, compared with those in quartile 1 who got the fewest steps per day (median 1,811), the risk of CVD was 20% lower in those in quartile 2, who got a median of 3,823 steps per day (hazard ratio, 0.80; 95% confidence interval, 0.69-0.93).

CVD risk was 38% lower in older adults in quartile 3 who got a median of 5,520 steps per day (HR, 0.62; 95% CI, 0.52-0.74) and 49% lower in those in quartile 4 who walked the most (a median of 9,259 steps per day; HR, 0.51; 95% CI, 0.41-0.63).

Restricting the analysis to individuals without known CVD at baseline showed similar results.

Among six studies that excluded adults with a history of CVD at baseline, compared with the lowest quartile, the HR for incident CVD events was 0.74 (95% CI, 0.60-0.91) in the second quartile, 0.60 (95% CI, 0.47-0.77) in the third quartile, and 0.55 (95% CI, 0.40-0.76) in the fourth quartile.

Despite the inverse association of steps with CVD in older adults, there was no association in younger adults. The researchers caution, however, that CVD is a disease of aging, and the follow-up period in these studies may not have been long enough to capture CVD incidence in younger adults.

Stepping rate (pace or cadence) was not associated with CVD risk beyond that of total steps per day. However, only four of the eight studies reported data on stepping rate, so this finding should be viewed as preliminary, Dr. Paluch and colleagues say.
 

Start small and go from there

Dr. Paluch said the take-home message from this study and numerous others is simple.

“Move more and sit less! Being physically active, by getting in your steps, is an important part of keeping your heart healthy,” she said in an interview.

For adults who are currently inactive, Dr. Paluch suggests finding small ways to get in a few more steps per day. “It does not need to be drastic changes. Consider a brief 5- to 10-minute walking break at lunch, taking the stairs, or playing a game of hide and seek with the grandchildren,” Dr. Paluch advised.

“For adults starting at 3,000 steps a day, set a goal of 4,000, and then 5,000. Each improvement can lead to better heart health,” Dr. Paluch said. “And for those who are already active, keep it up, as there are benefits with higher volumes of steps per day as well.”

Support for this research was provided by the Intergovernmental Personnel Act Agreement through the Centers for Disease Control and Prevention. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of young children unintentionally exposed to edible cannabis products in the United States jumped 1,375% over a 5-year period, according to a new analysis of data from poison control centers.

In 2017, centers received 207 reports of children aged 5 years and younger who ingested edible cannabis. In 2021, 3,054 such cases were reported, according to the study, which was published online in Pediatrics.

Many of the children experienced clinical effects, such as depression of the central nervous system, impaired coordination, confusion, agitation, an increase in heart rate, or dilated pupils. No deaths were reported.

“These exposures can cause significant toxicity and are responsible for an increasing number of hospitalizations,” study coauthor Marit S. Tweet, MD, of Southern Illinois University, Springfield, and colleagues wrote.

About 97% of the exposures occurred in residences – 90% at the child’s own home – and about half of the cases involved 2- and 3-year-olds, they noted.
 

Examining national trends

Twenty-one states have approved recreational cannabis for people aged 21 years and older.

Prior research has shown that calls to poison centers and visits to emergency departments for pediatric cannabis consumption increased in certain states after the drug became legal in those jurisdictions.

To assess national trends, Dr. Tweet’s group analyzed cases in the National Poison Data System, which tracks potentially toxic exposures reported to poison control centers in the United States.

During the 5-year period, they identified 7,043 exposures to edible cannabis by children younger than age 6. In 2.2% of the cases, the drug had a major effect, defined as being either life-threatening or causing residual disability. In 21.9% of cases, the effect was considered to be moderate, with symptoms that were more pronounced, prolonged, or systemic than minor effects.

About 8% of the children were admitted to critical care units; 14.6% were admitted to non–critical care units.

Of 4,827 cases for which there was information about the clinical effects of the exposure and therapies used, 70% involved CNS depression, including 1.9% with “more severe CNS effects, including major CNS depression or coma,” according to the report.

Patients also experienced ataxia (7.4%), agitation (7.1%), confusion (6.1%), tremor (2%), and seizures (1.6%). Other common symptoms included tachycardia (11.4%), vomiting (9.5%), mydriasis (5.9%), and respiratory depression (3.1%).

Treatments for the exposures included intravenous fluids (20.7%), food or snacks (10.3%), and oxygen therapy (4%). Some patients also received naloxone (1.4%) or charcoal (2.1%).

“The total number of children requiring intubation during the study period was 35, or approximately 1 in 140,” the researchers reported. “Although this was a relatively rare occurrence, it is important for clinicians to be aware that life-threatening sequelae can develop and may necessitate invasive supportive care measures.”
 

Tempting and toxic

For toddlers, edible cannabis may be especially tempting and toxic. Edibles can “resemble common treats such as candies, chocolates, cookies, or other baked goods,” the researchers wrote. Children would not recognize, for example, that one chocolate bar might contain multiple 10-mg servings of tetrahydrocannabinol intended for adults.

Poison centers have been fielding more calls about edible cannabis use by older children, as well.

Adrienne Hughes, MD, assistant professor of emergency medicine at Oregon Health and Science University, Portland, recently found that many cases of intentional misuse and abuse by adolescents involve edible forms of cannabis.

“While marijuana carries a low risk for severe toxicity, it can be inebriating to the point of poor judgment, risk of falls or other injury, and occasionally a panic reaction in the novice user and unsuspecting children who accidentally ingest these products,” Dr. Hughes said in an interview.

Measures to keep edibles away from children could include changing how the products are packaged, limiting the maximum dose of drug per package, and educating the public about the risks to children, Dr. Tweet’s group wrote. They highlighted a 2019 position statement from the American College of Medical Toxicology that includes recommendations for responsible storage habits.

Dr. Hughes echoed one suggestion that is mentioned in the position statement: Parents should consider keeping their cannabis products locked up.

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of young children unintentionally exposed to edible cannabis products in the United States jumped 1,375% over a 5-year period, according to a new analysis of data from poison control centers.

In 2017, centers received 207 reports of children aged 5 years and younger who ingested edible cannabis. In 2021, 3,054 such cases were reported, according to the study, which was published online in Pediatrics.

Many of the children experienced clinical effects, such as depression of the central nervous system, impaired coordination, confusion, agitation, an increase in heart rate, or dilated pupils. No deaths were reported.

“These exposures can cause significant toxicity and are responsible for an increasing number of hospitalizations,” study coauthor Marit S. Tweet, MD, of Southern Illinois University, Springfield, and colleagues wrote.

About 97% of the exposures occurred in residences – 90% at the child’s own home – and about half of the cases involved 2- and 3-year-olds, they noted.
 

Examining national trends

Twenty-one states have approved recreational cannabis for people aged 21 years and older.

Prior research has shown that calls to poison centers and visits to emergency departments for pediatric cannabis consumption increased in certain states after the drug became legal in those jurisdictions.

To assess national trends, Dr. Tweet’s group analyzed cases in the National Poison Data System, which tracks potentially toxic exposures reported to poison control centers in the United States.

During the 5-year period, they identified 7,043 exposures to edible cannabis by children younger than age 6. In 2.2% of the cases, the drug had a major effect, defined as being either life-threatening or causing residual disability. In 21.9% of cases, the effect was considered to be moderate, with symptoms that were more pronounced, prolonged, or systemic than minor effects.

About 8% of the children were admitted to critical care units; 14.6% were admitted to non–critical care units.

Of 4,827 cases for which there was information about the clinical effects of the exposure and therapies used, 70% involved CNS depression, including 1.9% with “more severe CNS effects, including major CNS depression or coma,” according to the report.

Patients also experienced ataxia (7.4%), agitation (7.1%), confusion (6.1%), tremor (2%), and seizures (1.6%). Other common symptoms included tachycardia (11.4%), vomiting (9.5%), mydriasis (5.9%), and respiratory depression (3.1%).

Treatments for the exposures included intravenous fluids (20.7%), food or snacks (10.3%), and oxygen therapy (4%). Some patients also received naloxone (1.4%) or charcoal (2.1%).

“The total number of children requiring intubation during the study period was 35, or approximately 1 in 140,” the researchers reported. “Although this was a relatively rare occurrence, it is important for clinicians to be aware that life-threatening sequelae can develop and may necessitate invasive supportive care measures.”
 

Tempting and toxic

For toddlers, edible cannabis may be especially tempting and toxic. Edibles can “resemble common treats such as candies, chocolates, cookies, or other baked goods,” the researchers wrote. Children would not recognize, for example, that one chocolate bar might contain multiple 10-mg servings of tetrahydrocannabinol intended for adults.

Poison centers have been fielding more calls about edible cannabis use by older children, as well.

Adrienne Hughes, MD, assistant professor of emergency medicine at Oregon Health and Science University, Portland, recently found that many cases of intentional misuse and abuse by adolescents involve edible forms of cannabis.

“While marijuana carries a low risk for severe toxicity, it can be inebriating to the point of poor judgment, risk of falls or other injury, and occasionally a panic reaction in the novice user and unsuspecting children who accidentally ingest these products,” Dr. Hughes said in an interview.

Measures to keep edibles away from children could include changing how the products are packaged, limiting the maximum dose of drug per package, and educating the public about the risks to children, Dr. Tweet’s group wrote. They highlighted a 2019 position statement from the American College of Medical Toxicology that includes recommendations for responsible storage habits.

Dr. Hughes echoed one suggestion that is mentioned in the position statement: Parents should consider keeping their cannabis products locked up.

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of young children unintentionally exposed to edible cannabis products in the United States jumped 1,375% over a 5-year period, according to a new analysis of data from poison control centers.

In 2017, centers received 207 reports of children aged 5 years and younger who ingested edible cannabis. In 2021, 3,054 such cases were reported, according to the study, which was published online in Pediatrics.

Many of the children experienced clinical effects, such as depression of the central nervous system, impaired coordination, confusion, agitation, an increase in heart rate, or dilated pupils. No deaths were reported.

“These exposures can cause significant toxicity and are responsible for an increasing number of hospitalizations,” study coauthor Marit S. Tweet, MD, of Southern Illinois University, Springfield, and colleagues wrote.

About 97% of the exposures occurred in residences – 90% at the child’s own home – and about half of the cases involved 2- and 3-year-olds, they noted.
 

Examining national trends

Twenty-one states have approved recreational cannabis for people aged 21 years and older.

Prior research has shown that calls to poison centers and visits to emergency departments for pediatric cannabis consumption increased in certain states after the drug became legal in those jurisdictions.

To assess national trends, Dr. Tweet’s group analyzed cases in the National Poison Data System, which tracks potentially toxic exposures reported to poison control centers in the United States.

During the 5-year period, they identified 7,043 exposures to edible cannabis by children younger than age 6. In 2.2% of the cases, the drug had a major effect, defined as being either life-threatening or causing residual disability. In 21.9% of cases, the effect was considered to be moderate, with symptoms that were more pronounced, prolonged, or systemic than minor effects.

About 8% of the children were admitted to critical care units; 14.6% were admitted to non–critical care units.

Of 4,827 cases for which there was information about the clinical effects of the exposure and therapies used, 70% involved CNS depression, including 1.9% with “more severe CNS effects, including major CNS depression or coma,” according to the report.

Patients also experienced ataxia (7.4%), agitation (7.1%), confusion (6.1%), tremor (2%), and seizures (1.6%). Other common symptoms included tachycardia (11.4%), vomiting (9.5%), mydriasis (5.9%), and respiratory depression (3.1%).

Treatments for the exposures included intravenous fluids (20.7%), food or snacks (10.3%), and oxygen therapy (4%). Some patients also received naloxone (1.4%) or charcoal (2.1%).

“The total number of children requiring intubation during the study period was 35, or approximately 1 in 140,” the researchers reported. “Although this was a relatively rare occurrence, it is important for clinicians to be aware that life-threatening sequelae can develop and may necessitate invasive supportive care measures.”
 

Tempting and toxic

For toddlers, edible cannabis may be especially tempting and toxic. Edibles can “resemble common treats such as candies, chocolates, cookies, or other baked goods,” the researchers wrote. Children would not recognize, for example, that one chocolate bar might contain multiple 10-mg servings of tetrahydrocannabinol intended for adults.

Poison centers have been fielding more calls about edible cannabis use by older children, as well.

Adrienne Hughes, MD, assistant professor of emergency medicine at Oregon Health and Science University, Portland, recently found that many cases of intentional misuse and abuse by adolescents involve edible forms of cannabis.

“While marijuana carries a low risk for severe toxicity, it can be inebriating to the point of poor judgment, risk of falls or other injury, and occasionally a panic reaction in the novice user and unsuspecting children who accidentally ingest these products,” Dr. Hughes said in an interview.

Measures to keep edibles away from children could include changing how the products are packaged, limiting the maximum dose of drug per package, and educating the public about the risks to children, Dr. Tweet’s group wrote. They highlighted a 2019 position statement from the American College of Medical Toxicology that includes recommendations for responsible storage habits.

Dr. Hughes echoed one suggestion that is mentioned in the position statement: Parents should consider keeping their cannabis products locked up.

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved semaglutide 2.4 mg (Wegovy), a once-weekly subcutaneous injection, for the additional indication of treating obesity in adolescents aged 12 years and older.

This is defined as those with an initial body mass index at or above the 95th percentile for age and sex (based on CDC growth charts). Semaglutide must be administered along with lifestyle intervention of a reduced calorie meal plan and increased physical activity.

Olivier Le Moal/Getty Images

When Wegovy was approved for use in adults with obesity in June 2021, it was labeled a “game changer.”

The new approval is based on the results of the STEP TEENS phase 3 trial of once-weekly 2.4 mg of semaglutide in adolescents 12- to <18 years old with obesity, the drug’s manufacturer, Novo Nordisk, announced in a press release.

In STEP TEENS, reported at Obesity Week 2022 in November, and simultaneously published in the New England Journal of Medicine, adolescents with obesity treated with semaglutide for 68 weeks had a 16.1% reduction in BMI compared with a 0.6% increase in BMI in those receiving placebo. Both groups also received lifestyle intervention. Mean weight loss was 15.3 kg (33.7 pounds) among teens on semaglutide, while those on placebo gained 2.4 kg (5.3 pounds).

At the time, Claudia K. Fox, MD, MPH, codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota – who was not involved with the research – told this news organization the results were “mind-blowing ... we are getting close to bariatric surgery results” in these adolescent patients with obesity.

Semaglutide is a GLP-1 agonist, as is a related agent, also from Novo Nordisk, liraglutide (Saxenda), a daily subcutaneous injection, which was approved for use in adolescents aged 12 and older in December 2020. Wegovy is the first weekly subcutaneous injection approved for use in adolescents.

Other agents approved for obesity in those older than 12 in the United States include the combination phentermine and topiramate extended-release capsules (Qsymia) in June 2022, and orlistat (Alli). Phentermine is approved for those aged 16 and older.  

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved semaglutide 2.4 mg (Wegovy), a once-weekly subcutaneous injection, for the additional indication of treating obesity in adolescents aged 12 years and older.

This is defined as those with an initial body mass index at or above the 95th percentile for age and sex (based on CDC growth charts). Semaglutide must be administered along with lifestyle intervention of a reduced calorie meal plan and increased physical activity.

Olivier Le Moal/Getty Images

When Wegovy was approved for use in adults with obesity in June 2021, it was labeled a “game changer.”

The new approval is based on the results of the STEP TEENS phase 3 trial of once-weekly 2.4 mg of semaglutide in adolescents 12- to <18 years old with obesity, the drug’s manufacturer, Novo Nordisk, announced in a press release.

In STEP TEENS, reported at Obesity Week 2022 in November, and simultaneously published in the New England Journal of Medicine, adolescents with obesity treated with semaglutide for 68 weeks had a 16.1% reduction in BMI compared with a 0.6% increase in BMI in those receiving placebo. Both groups also received lifestyle intervention. Mean weight loss was 15.3 kg (33.7 pounds) among teens on semaglutide, while those on placebo gained 2.4 kg (5.3 pounds).

At the time, Claudia K. Fox, MD, MPH, codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota – who was not involved with the research – told this news organization the results were “mind-blowing ... we are getting close to bariatric surgery results” in these adolescent patients with obesity.

Semaglutide is a GLP-1 agonist, as is a related agent, also from Novo Nordisk, liraglutide (Saxenda), a daily subcutaneous injection, which was approved for use in adolescents aged 12 and older in December 2020. Wegovy is the first weekly subcutaneous injection approved for use in adolescents.

Other agents approved for obesity in those older than 12 in the United States include the combination phentermine and topiramate extended-release capsules (Qsymia) in June 2022, and orlistat (Alli). Phentermine is approved for those aged 16 and older.  

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved semaglutide 2.4 mg (Wegovy), a once-weekly subcutaneous injection, for the additional indication of treating obesity in adolescents aged 12 years and older.

This is defined as those with an initial body mass index at or above the 95th percentile for age and sex (based on CDC growth charts). Semaglutide must be administered along with lifestyle intervention of a reduced calorie meal plan and increased physical activity.

Olivier Le Moal/Getty Images

When Wegovy was approved for use in adults with obesity in June 2021, it was labeled a “game changer.”

The new approval is based on the results of the STEP TEENS phase 3 trial of once-weekly 2.4 mg of semaglutide in adolescents 12- to <18 years old with obesity, the drug’s manufacturer, Novo Nordisk, announced in a press release.

In STEP TEENS, reported at Obesity Week 2022 in November, and simultaneously published in the New England Journal of Medicine, adolescents with obesity treated with semaglutide for 68 weeks had a 16.1% reduction in BMI compared with a 0.6% increase in BMI in those receiving placebo. Both groups also received lifestyle intervention. Mean weight loss was 15.3 kg (33.7 pounds) among teens on semaglutide, while those on placebo gained 2.4 kg (5.3 pounds).

At the time, Claudia K. Fox, MD, MPH, codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota – who was not involved with the research – told this news organization the results were “mind-blowing ... we are getting close to bariatric surgery results” in these adolescent patients with obesity.

Semaglutide is a GLP-1 agonist, as is a related agent, also from Novo Nordisk, liraglutide (Saxenda), a daily subcutaneous injection, which was approved for use in adolescents aged 12 and older in December 2020. Wegovy is the first weekly subcutaneous injection approved for use in adolescents.

Other agents approved for obesity in those older than 12 in the United States include the combination phentermine and topiramate extended-release capsules (Qsymia) in June 2022, and orlistat (Alli). Phentermine is approved for those aged 16 and older.  

A version of this article first appeared on Medscape.com.

In this current age of mass misinformation and disinformation on the Internet, a tongue-in-cheek study that evaluated beliefs and attitudes toward cancer among conspiracy theorists and people who oppose vaccinations has received some harsh criticism.

The study, entitled, “Everything Causes Cancer? Beliefs and Attitudes Towards Cancer Prevention Among Anti-Vaxxers, Flat Earthers, and Reptilian Conspiracists: Online Cross Sectional Survey,” was published in the Christmas 2022 issue of The British Medical Journal (BMJ).

The authors explain that they set out to evaluate “the patterns of beliefs about cancer among people who believed in conspiracies, rejected the COVID-19 vaccine, or preferred alternative medicine.”

They sought such people on social media and online chat platforms and asked them questions about real and mythical causes of cancer.

Almost half of survey participants agreed with the statement, “It seems like everything causes cancer.”

Overall, among all participants, awareness of the actual causes of cancer was greater than awareness of the mythical causes of cancer, the authors report. However, awareness of the actual causes of cancer was lower among the unvaccinated and members of conspiracy groups than among their counterparts.

The authors are concerned that their findings suggest “a direct connection between digital misinformation and consequent potential erroneous health decisions, which may represent a further preventable fraction of cancer.”
 

Backlash and criticism

The study “highlights the difficulty society encounters in distinguishing the actual causes of cancer from mythical causes,” The BMJ commented on Twitter.

However, both the study and the journal received some backlash.

This is a “horrible article seeking to smear people with concerns about COVID vaccines,” commented Clare Craig, a British consultant pathologist who specializes in cancer diagnostics.

The study and its methodology were also harshly criticized on Twitter by Normal Fenton, professor of risk information management at the Queen Mary University of London.

The senior author of the study, Laura Costas, a medical epidemiologist with the Catalan Institute of Oncology, Barcelona, told this news organization that the naysayers on social media, many of whom focused their comments on the COVID-19 vaccine, prove the purpose of the study – that misinformation spreads widely on the internet.

“Most comments focused on spreading COVID-19 myths, which were not the direct subject of the study, and questioned the motivations of BMJ authors and the scientific community, assuming they had a common malevolent hidden agenda,” Ms. Costas said.

“They stated the need of having critical thinking, a trait in common with the scientific method, but dogmatically dismissed any information that comes from official sources,” she added.

Ms. Costas commented that “society encounters difficulty in differentiating actual from mythical causes of cancer owing to mass information. We therefore planned this study with a certain satire, which is in line with the essence of The BMJ Christmas issue.”

The BMJ has a long history of publishing a lighthearted Christmas edition full of original, satirical, and nontraditional studies. Previous years have seen studies that explored potential harms from holly and ivy, survival time of chocolates on hospital wards, and the question, “Were James Bond’s drinks shaken because of alcohol induced tremor?”
 

Study details

Ms. Costas and colleagues sought participants for their survey from online forums that included 4chan and Reddit, which are known for their controversial content posted by anonymous users. Data were also collected from ForoCoches and HispaChan, well-known Spanish online forums. These online sites were intentionally chosen because researchers thought “conspiracy beliefs would be more prevalent,” according to Ms. Costas.

Across the multiple forums, there were 1,494 participants. Of these, 209 participants were unvaccinated against COVID-19, 112 preferred alternatives rather than conventional medicine, and 62 reported that they believed the earth was flat or believed that humanoids take reptilian forms to manipulate human societies.

The team then sought to assess beliefs about actual and mythical (nonestablished) causes of cancer by presenting the participants with the closed risk factor questions on two validated scales – the Cancer Awareness Measure (CAM) and CAM–Mythical Causes Scale (CAM-MYCS).

Responses to both were recorded on a five-point scale; answers ranged from “strongly disagree” to “strongly agree.”

The CAM assesses cancer risk perceptions of 11 established risk factors for cancer: smoking actively or passively, consuming alcohol, low levels of physical activity, consuming red or processed meat, getting sunburnt as a child, family history of cancer, human papillomavirus infection, being overweight, age greater than or equal to 70 years, and low vegetable and fruit consumption.

The CAM-MYCS measure includes 12 questions on risk perceptions of mythical causes of cancer – nonestablished causes that are commonly believed to cause cancer but for which there is no supporting scientific evidence, the authors explain. These items include drinking from plastic bottles; eating food containing artificial sweeteners or additives and genetically modified food; using microwave ovens, aerosol containers, mobile phones, and cleaning products; living near power lines; feeling stressed; experiencing physical trauma; and being exposed to electromagnetic frequencies/non-ionizing radiation, such as wi-fi networks, radio, and television.

The most endorsed mythical causes of cancer were eating food containing additives (63.9%) or sweeteners (50.7%), feeling stressed (59.7%), and eating genetically modified foods (38.4%).

A version of this article first appeared on Medscape.com.

In this current age of mass misinformation and disinformation on the Internet, a tongue-in-cheek study that evaluated beliefs and attitudes toward cancer among conspiracy theorists and people who oppose vaccinations has received some harsh criticism.

The study, entitled, “Everything Causes Cancer? Beliefs and Attitudes Towards Cancer Prevention Among Anti-Vaxxers, Flat Earthers, and Reptilian Conspiracists: Online Cross Sectional Survey,” was published in the Christmas 2022 issue of The British Medical Journal (BMJ).

The authors explain that they set out to evaluate “the patterns of beliefs about cancer among people who believed in conspiracies, rejected the COVID-19 vaccine, or preferred alternative medicine.”

They sought such people on social media and online chat platforms and asked them questions about real and mythical causes of cancer.

Almost half of survey participants agreed with the statement, “It seems like everything causes cancer.”

Overall, among all participants, awareness of the actual causes of cancer was greater than awareness of the mythical causes of cancer, the authors report. However, awareness of the actual causes of cancer was lower among the unvaccinated and members of conspiracy groups than among their counterparts.

The authors are concerned that their findings suggest “a direct connection between digital misinformation and consequent potential erroneous health decisions, which may represent a further preventable fraction of cancer.”
 

Backlash and criticism

The study “highlights the difficulty society encounters in distinguishing the actual causes of cancer from mythical causes,” The BMJ commented on Twitter.

However, both the study and the journal received some backlash.

This is a “horrible article seeking to smear people with concerns about COVID vaccines,” commented Clare Craig, a British consultant pathologist who specializes in cancer diagnostics.

The study and its methodology were also harshly criticized on Twitter by Normal Fenton, professor of risk information management at the Queen Mary University of London.

The senior author of the study, Laura Costas, a medical epidemiologist with the Catalan Institute of Oncology, Barcelona, told this news organization that the naysayers on social media, many of whom focused their comments on the COVID-19 vaccine, prove the purpose of the study – that misinformation spreads widely on the internet.

“Most comments focused on spreading COVID-19 myths, which were not the direct subject of the study, and questioned the motivations of BMJ authors and the scientific community, assuming they had a common malevolent hidden agenda,” Ms. Costas said.

“They stated the need of having critical thinking, a trait in common with the scientific method, but dogmatically dismissed any information that comes from official sources,” she added.

Ms. Costas commented that “society encounters difficulty in differentiating actual from mythical causes of cancer owing to mass information. We therefore planned this study with a certain satire, which is in line with the essence of The BMJ Christmas issue.”

The BMJ has a long history of publishing a lighthearted Christmas edition full of original, satirical, and nontraditional studies. Previous years have seen studies that explored potential harms from holly and ivy, survival time of chocolates on hospital wards, and the question, “Were James Bond’s drinks shaken because of alcohol induced tremor?”
 

Study details

Ms. Costas and colleagues sought participants for their survey from online forums that included 4chan and Reddit, which are known for their controversial content posted by anonymous users. Data were also collected from ForoCoches and HispaChan, well-known Spanish online forums. These online sites were intentionally chosen because researchers thought “conspiracy beliefs would be more prevalent,” according to Ms. Costas.

Across the multiple forums, there were 1,494 participants. Of these, 209 participants were unvaccinated against COVID-19, 112 preferred alternatives rather than conventional medicine, and 62 reported that they believed the earth was flat or believed that humanoids take reptilian forms to manipulate human societies.

The team then sought to assess beliefs about actual and mythical (nonestablished) causes of cancer by presenting the participants with the closed risk factor questions on two validated scales – the Cancer Awareness Measure (CAM) and CAM–Mythical Causes Scale (CAM-MYCS).

Responses to both were recorded on a five-point scale; answers ranged from “strongly disagree” to “strongly agree.”

The CAM assesses cancer risk perceptions of 11 established risk factors for cancer: smoking actively or passively, consuming alcohol, low levels of physical activity, consuming red or processed meat, getting sunburnt as a child, family history of cancer, human papillomavirus infection, being overweight, age greater than or equal to 70 years, and low vegetable and fruit consumption.

The CAM-MYCS measure includes 12 questions on risk perceptions of mythical causes of cancer – nonestablished causes that are commonly believed to cause cancer but for which there is no supporting scientific evidence, the authors explain. These items include drinking from plastic bottles; eating food containing artificial sweeteners or additives and genetically modified food; using microwave ovens, aerosol containers, mobile phones, and cleaning products; living near power lines; feeling stressed; experiencing physical trauma; and being exposed to electromagnetic frequencies/non-ionizing radiation, such as wi-fi networks, radio, and television.

The most endorsed mythical causes of cancer were eating food containing additives (63.9%) or sweeteners (50.7%), feeling stressed (59.7%), and eating genetically modified foods (38.4%).

A version of this article first appeared on Medscape.com.

In this current age of mass misinformation and disinformation on the Internet, a tongue-in-cheek study that evaluated beliefs and attitudes toward cancer among conspiracy theorists and people who oppose vaccinations has received some harsh criticism.

The study, entitled, “Everything Causes Cancer? Beliefs and Attitudes Towards Cancer Prevention Among Anti-Vaxxers, Flat Earthers, and Reptilian Conspiracists: Online Cross Sectional Survey,” was published in the Christmas 2022 issue of The British Medical Journal (BMJ).

The authors explain that they set out to evaluate “the patterns of beliefs about cancer among people who believed in conspiracies, rejected the COVID-19 vaccine, or preferred alternative medicine.”

They sought such people on social media and online chat platforms and asked them questions about real and mythical causes of cancer.

Almost half of survey participants agreed with the statement, “It seems like everything causes cancer.”

Overall, among all participants, awareness of the actual causes of cancer was greater than awareness of the mythical causes of cancer, the authors report. However, awareness of the actual causes of cancer was lower among the unvaccinated and members of conspiracy groups than among their counterparts.

The authors are concerned that their findings suggest “a direct connection between digital misinformation and consequent potential erroneous health decisions, which may represent a further preventable fraction of cancer.”
 

Backlash and criticism

The study “highlights the difficulty society encounters in distinguishing the actual causes of cancer from mythical causes,” The BMJ commented on Twitter.

However, both the study and the journal received some backlash.

This is a “horrible article seeking to smear people with concerns about COVID vaccines,” commented Clare Craig, a British consultant pathologist who specializes in cancer diagnostics.

The study and its methodology were also harshly criticized on Twitter by Normal Fenton, professor of risk information management at the Queen Mary University of London.

The senior author of the study, Laura Costas, a medical epidemiologist with the Catalan Institute of Oncology, Barcelona, told this news organization that the naysayers on social media, many of whom focused their comments on the COVID-19 vaccine, prove the purpose of the study – that misinformation spreads widely on the internet.

“Most comments focused on spreading COVID-19 myths, which were not the direct subject of the study, and questioned the motivations of BMJ authors and the scientific community, assuming they had a common malevolent hidden agenda,” Ms. Costas said.

“They stated the need of having critical thinking, a trait in common with the scientific method, but dogmatically dismissed any information that comes from official sources,” she added.

Ms. Costas commented that “society encounters difficulty in differentiating actual from mythical causes of cancer owing to mass information. We therefore planned this study with a certain satire, which is in line with the essence of The BMJ Christmas issue.”

The BMJ has a long history of publishing a lighthearted Christmas edition full of original, satirical, and nontraditional studies. Previous years have seen studies that explored potential harms from holly and ivy, survival time of chocolates on hospital wards, and the question, “Were James Bond’s drinks shaken because of alcohol induced tremor?”
 

Study details

Ms. Costas and colleagues sought participants for their survey from online forums that included 4chan and Reddit, which are known for their controversial content posted by anonymous users. Data were also collected from ForoCoches and HispaChan, well-known Spanish online forums. These online sites were intentionally chosen because researchers thought “conspiracy beliefs would be more prevalent,” according to Ms. Costas.

Across the multiple forums, there were 1,494 participants. Of these, 209 participants were unvaccinated against COVID-19, 112 preferred alternatives rather than conventional medicine, and 62 reported that they believed the earth was flat or believed that humanoids take reptilian forms to manipulate human societies.

The team then sought to assess beliefs about actual and mythical (nonestablished) causes of cancer by presenting the participants with the closed risk factor questions on two validated scales – the Cancer Awareness Measure (CAM) and CAM–Mythical Causes Scale (CAM-MYCS).

Responses to both were recorded on a five-point scale; answers ranged from “strongly disagree” to “strongly agree.”

The CAM assesses cancer risk perceptions of 11 established risk factors for cancer: smoking actively or passively, consuming alcohol, low levels of physical activity, consuming red or processed meat, getting sunburnt as a child, family history of cancer, human papillomavirus infection, being overweight, age greater than or equal to 70 years, and low vegetable and fruit consumption.

The CAM-MYCS measure includes 12 questions on risk perceptions of mythical causes of cancer – nonestablished causes that are commonly believed to cause cancer but for which there is no supporting scientific evidence, the authors explain. These items include drinking from plastic bottles; eating food containing artificial sweeteners or additives and genetically modified food; using microwave ovens, aerosol containers, mobile phones, and cleaning products; living near power lines; feeling stressed; experiencing physical trauma; and being exposed to electromagnetic frequencies/non-ionizing radiation, such as wi-fi networks, radio, and television.

The most endorsed mythical causes of cancer were eating food containing additives (63.9%) or sweeteners (50.7%), feeling stressed (59.7%), and eating genetically modified foods (38.4%).

A version of this article first appeared on Medscape.com.

Leading cardiology societies have issued a “call for action” on a global scale to reinvent randomized clinical trials fit for the 21st century.

“Randomized trials are an essential tool for reliably assessing the effects of treatments, but they have become too costly and too burdensome,” first author Louise Bowman, University of Oxford, England, told this news organization. “We urgently need to modernize our approach to clinical trials in order to continue to improve patient care.”

The joint opinion is from the European Society of Cardiology, the American Heart Association, the American College of Cardiology, and the World Heart Federation. It was simultaneously published online in the European Heart Journal, Circulation, Journal of the American College of Cardiology, and Global Heart.

The authors note that the availability of large-scale “real-world” data is increasingly being touted as a way to bypass the challenges of conducting randomized trials. Yet, observational analyses of real-world data “are not a suitable alternative to randomization,” Prof. Bowman said.

Cardiology has historically led the way in transforming clinical practice with groundbreaking “mega-trials,” such as the International Study of Infarct Survival (ISIS), Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto (GISSI), and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO).

But over the past 25 years, there has been a huge increase in the rules and related bureaucracy governing clinical trials, which hinders the ability to conduct trials swiftly and affordably, the authors point out.

The COVID-19 pandemic has shown that important clinical trials can be performed quickly and efficiently in busy hospitals, they note.

“The RECOVERY trial in COVID-19 has been an excellent example of this, with results that are estimated to have saved around 1 million lives worldwide within just 1 year,” Prof. Bowman told this news organization.

A Good Clinical Trials Collaborative made up of key stakeholders recently developed new guidelines designed to promote better, more efficient randomized controlled trials.

“If widely adopted and used alongside valuable 21st century electronic health records, we could transform the clinical trials landscape and do many more high-quality trials very cost-effectively,” Prof. Bowman said.

“Widespread adoption and implementation of the revised guidelines will require collaboration with a wide range of national and international organizations, including patient, professional, academic, and industry groups, funders and government organizations, and ethics, health policy, and regulatory bodies,” Prof. Bowman acknowledged.

“This is work that the Good Clinical Trials Collaborative is leading. It is hoped that this endorsement by the joint cardiovascular societies will increase awareness and provide valuable support to his important work,” she added.

No commercial funding was received. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Leading cardiology societies have issued a “call for action” on a global scale to reinvent randomized clinical trials fit for the 21st century.

“Randomized trials are an essential tool for reliably assessing the effects of treatments, but they have become too costly and too burdensome,” first author Louise Bowman, University of Oxford, England, told this news organization. “We urgently need to modernize our approach to clinical trials in order to continue to improve patient care.”

The joint opinion is from the European Society of Cardiology, the American Heart Association, the American College of Cardiology, and the World Heart Federation. It was simultaneously published online in the European Heart Journal, Circulation, Journal of the American College of Cardiology, and Global Heart.

The authors note that the availability of large-scale “real-world” data is increasingly being touted as a way to bypass the challenges of conducting randomized trials. Yet, observational analyses of real-world data “are not a suitable alternative to randomization,” Prof. Bowman said.

Cardiology has historically led the way in transforming clinical practice with groundbreaking “mega-trials,” such as the International Study of Infarct Survival (ISIS), Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto (GISSI), and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO).

But over the past 25 years, there has been a huge increase in the rules and related bureaucracy governing clinical trials, which hinders the ability to conduct trials swiftly and affordably, the authors point out.

The COVID-19 pandemic has shown that important clinical trials can be performed quickly and efficiently in busy hospitals, they note.

“The RECOVERY trial in COVID-19 has been an excellent example of this, with results that are estimated to have saved around 1 million lives worldwide within just 1 year,” Prof. Bowman told this news organization.

A Good Clinical Trials Collaborative made up of key stakeholders recently developed new guidelines designed to promote better, more efficient randomized controlled trials.

“If widely adopted and used alongside valuable 21st century electronic health records, we could transform the clinical trials landscape and do many more high-quality trials very cost-effectively,” Prof. Bowman said.

“Widespread adoption and implementation of the revised guidelines will require collaboration with a wide range of national and international organizations, including patient, professional, academic, and industry groups, funders and government organizations, and ethics, health policy, and regulatory bodies,” Prof. Bowman acknowledged.

“This is work that the Good Clinical Trials Collaborative is leading. It is hoped that this endorsement by the joint cardiovascular societies will increase awareness and provide valuable support to his important work,” she added.

No commercial funding was received. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Leading cardiology societies have issued a “call for action” on a global scale to reinvent randomized clinical trials fit for the 21st century.

“Randomized trials are an essential tool for reliably assessing the effects of treatments, but they have become too costly and too burdensome,” first author Louise Bowman, University of Oxford, England, told this news organization. “We urgently need to modernize our approach to clinical trials in order to continue to improve patient care.”

The joint opinion is from the European Society of Cardiology, the American Heart Association, the American College of Cardiology, and the World Heart Federation. It was simultaneously published online in the European Heart Journal, Circulation, Journal of the American College of Cardiology, and Global Heart.

The authors note that the availability of large-scale “real-world” data is increasingly being touted as a way to bypass the challenges of conducting randomized trials. Yet, observational analyses of real-world data “are not a suitable alternative to randomization,” Prof. Bowman said.

Cardiology has historically led the way in transforming clinical practice with groundbreaking “mega-trials,” such as the International Study of Infarct Survival (ISIS), Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto (GISSI), and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO).

But over the past 25 years, there has been a huge increase in the rules and related bureaucracy governing clinical trials, which hinders the ability to conduct trials swiftly and affordably, the authors point out.

The COVID-19 pandemic has shown that important clinical trials can be performed quickly and efficiently in busy hospitals, they note.

“The RECOVERY trial in COVID-19 has been an excellent example of this, with results that are estimated to have saved around 1 million lives worldwide within just 1 year,” Prof. Bowman told this news organization.

A Good Clinical Trials Collaborative made up of key stakeholders recently developed new guidelines designed to promote better, more efficient randomized controlled trials.

“If widely adopted and used alongside valuable 21st century electronic health records, we could transform the clinical trials landscape and do many more high-quality trials very cost-effectively,” Prof. Bowman said.

“Widespread adoption and implementation of the revised guidelines will require collaboration with a wide range of national and international organizations, including patient, professional, academic, and industry groups, funders and government organizations, and ethics, health policy, and regulatory bodies,” Prof. Bowman acknowledged.

“This is work that the Good Clinical Trials Collaborative is leading. It is hoped that this endorsement by the joint cardiovascular societies will increase awareness and provide valuable support to his important work,” she added.

No commercial funding was received. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.

Pemphigus is a group of autoimmune blistering diseases characterized by the development of painful and flaccid blisters on the skin and/or mucous membranes. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are 2 major subtypes and can be distinguished by the location of blister formation or the specificity of autoantibodies directed against different desmogleins.^1,2 Although rare, pemphigus is considered a serious and life-threatening condition with a great impact on quality of life (QOL) due to disease symptoms (eg, painful lesions, physical appearance of skin lesions) as well as treatment complications (eg, adverse drug effects, cost of treatment).^3-6 Moreover, the physical and psychological effects can lead to marked functional morbidity and work-related disability during patients’ productive years.⁷ Therefore, affected individuals usually have a remarkably compromised health-related quality of life (HRQOL).⁸ Effective treatments may considerably improve the QOL of patients with pemphigus.⁶

Despite the available treatment options, finding the best regimen for pemphigus remains a challenge. Corticosteroids are assumed to be the main treatment, though they have considerable side effects.^9,10 Adjuvant therapies are used to suppress or modulate immune responses, leading to remission with the least possible need for corticosteroids. Finding an optimal steroid-sparing agent has been the aim of research, and biologic agents seem to be the best option.⁸ Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown great promise in several studies of its clinical efficacy and has become a first-line treatment in new guidelines.^11-14 Rituximab treatment has been associated with notable improvement in physician-assessed outcome measures with a favorable safety profile in patients with pemphigus.^11-15 However, it is important to assess response to treatment from a patient’s perspective through the use of outcome-assessment measures that encompass patient-reported outcomes to reflect the complete patient experience and establish the overall impact of RTX as well as its likelihood of acceptance by patients with pemphigus.

In our study, we compared clinical outcomes and HRQOL through the use of disease-specific measures as well as comprehensive generic health status measures among patients with PV and PF who received RTX treatment 3 months earlier and those who received RTX in the last 2 weeks. The clinical relevance of the patient-reported outcomes is discussed.

MATERIALS AND METHODS

Study Design

We conducted a single-center cross-sectional study of 96 patients with pemphigus aged 18 to 65 years of either sex who were willing to participate in this study. Patients with a confirmed diagnosis of PV or PF who received RTX 3 months earlier or in the last 2 weeks were enrolled in the study. Patients were identified using Dermatry.ir, an archiving software that contains patients’ medical data. Exclusion criteria included lack of sufficient knowledge of the concepts of the questionnaires as well as age younger than 16 years. The study was conducted from October 2019 to April 2020 by the Autoimmune Bullous Disease Research Center at Razi Hospital in Tehran, Iran, which is the main dermatology-specific center and teaching hospital of Iran. The study protocol was approved by the relevant ethics committee.

Patients were categorized into 2 groups: (1) those who received RTX 3 months earlier (3M group); and (2) those who received RTX in the last 2 weeks (R group).

After an explanation of the study to participants, informed written consent was signed by each patient, and their personal data (eg, age, sex, education, marital status, smoking status), as well as clinical data (eg, type of pemphigus, duration of disease, site of onset, prednisolone dosage, presence of Nikolsky sign, anti-DSG1 and anti-DSG3 values, Pemphigus Disease Area Index [PDAI] score, RTX treatment protocol); any known comorbidities such as hypertension, diabetes mellitus, or morbid obesity; and any chronic pulmonary, cardiac, endocrinologic, renal, or hepatic condition, were collected and recorded in a predefined Case Record.

Patient-Reported Outcome Measures

The effect of RTX on QOL in patients with pemphigus was assessed using 2 HRQOL instruments: (1) a general health status indicator, the 36-Item Short Form Survey (SF-36), and (2) a validated, Persian version of a dermatology-specific questionnaire, Dermatology Life Quality Index (DLQI). The questionnaires were completed by each patient or by an assistant if needed.

The SF-36 is a widely used 36-item questionnaire measuring functional health and well-being across 8 domains—mental health, pain, physical function, role emotional, role physical, social functioning, vitality, and general health perception—with scores for each ranging from 0 to 100. The physical component scores (PCSs) and mental component scores (MCSs) were derived from these 8 subscales, each ranging from 0 to 400, with higher scores indicating better health status.⁶

The DLQI, one of the most frequently used QOL measures in dermatology, contains 10 questions, each referring to the prior week and classified in the following 6 subscales: symptoms and feelings, daily activities, leisure, personal relationships, work and school, and treatment.¹⁶ The total score ranges from 0 (no impact) to 30 (very high impact), with a higher score indicating a lower QOL (eTable 1). The minimal clinically important difference (MCD) for the DLQI was considered to be 2- to 5-point changes in prior studies.^17,18 In this study, we used an MCD of a 5-point change or more between study groups.

Moreover, the patient general assessment (PGA) of disease severity was identified using a 3-point scale (1=mild, 2=moderate, 3=severe).

Statistical Analysis

Data were analyzed using SPSS Statistics version 23. P≤.05 was considered significant. Mean and SD were calculated for descriptive data. The t test, Fisher exact test, analysis of variance, multiple regression analysis, and logistic regression analysis were used to identify the relationship between variables.

RESULTS

Patient Characteristics

A total of 96 patients were enrolled in this study. The mean (SD) age of participants was 41.42 (15.1) years (range, 18–58 years). Of 96 patients whose data were included, 55 (57.29%) patients had received RTX 3 months earlier (3M group) and 41 (42.71%) received RTX in the last 2 weeks (R group). A summary of study patient characteristics in each group is provided in eTable 2. There was no significant difference between the 2 groups in terms of age, sex, type of pemphigus, marital status, education, positive Nikolsky sign, smoking status, existence of comorbidities, site of lesions, and RTX treatment protocol. However, a significant difference was found for duration of disease (P=.0124) and mean prednisolone dosage (P=.001) as well as severity of disease measured by PDAI score (P=.003) and anti-DSG1 (P=.003) and anti-DSG3 (P=.021) values.

Patient-Reported Outcomes

Physical and mental component scores are summarized in eTable 3. Generally, SF-36 scores were improved with RTX treatment in all dimensions except for mental health, though these differences were not statistically significant, with the greatest mean improvement in the role physical index (75.45 in the 3M group vs 53.04 in the R group; P=.009). Mean SF-36 PCS and MCS scores were higher in the 3M group vs the R group, though the difference in MCS score did not reach the level of significance (eTable 3).

Mean DLQI scores in the R and 3M groups were 12.31 and 6.96, respectively, indicating a considerable burden on HRQOL in both groups. However, a statistically significant difference between these values was seen that also was clinically meaningful, indicating a significant improvement of QOL in patients receiving RTX 3 months earlier (P=.005)(eTable 3).

The PGA scores indicated that patients in the 3M group were significantly more likely to report less severe disease vs the R group (P=.008)(eTable 3).

Multivariate Analysis—Effect of the patient characteristics and some disease features on indices of QOL was evaluated using the multiple linear regression model. eTable 4 shows the P values of those analyses.

COMMENT

Pemphigus is a chronic disabling disease with notable QOL impairment due to disease burden as well as the need for long-term use of immunosuppressive agents during the disease course. To study the effect of RTX on QOL of patients with pemphigus, we compared 2 sets of patients. Prior studies have shown that clinically significant effects of RTX take 4 to 12 weeks to appear.^19,20 Therefore, we selected patients who received RTX 3 months earlier to measure their HRQOL indices and compare them with patients who had received RTX in the last 2 weeks as a control group to investigate the effect of RTX intrinsically, as this was the focus of this study.

In our study, one of the research tools was the DLQI. Healthy patients typically have an average score of 0.5.²¹ The mean DLQI score of the patients in R group was 12.31, which was similar to prior analysis⁸ and reflects a substantial burden of disease comparable to atopic dermatitis and psoriasis.^21,22 In patients in the 3M group, the mean DLQI score was lower than the R group (6.96 vs 12.31), indicating a significant (P=.005) and clinically meaningful improvement in QOL of patients due to the dramatic therapeutic effect of RTX. However, this score indicated a moderate effect on HRQOL, even in the context of clinical improvement due to RTX treatment, which may reflect that the short duration of treatment in the 3M group was a limitation of this study. Although the 12-week treatment duration was comparable with other studies^19,20 and major differences in objective measures of treatment efficacy were found in PDAI as well as anti-DSG1 and anti-DSG3 values, longer treatment duration may be needed for a more comprehensive assessment of the benefit of RTX on HRQOL indices in patients with pemphigus.

Based on results of the SF-36 questionnaire, PCS and MCS scores were not substantially impaired in the R group considering the fact that a mean score of 50 has been articulated as a normative value for all scales.²³ These data demonstrated the importance of using a dermatologic-specific instrument such as the DLQI instead of a general questionnaire to assess QOL in patients with pemphigus. However, better indices were reported with RTX treatment in the 3 SF-36 domains—role physical (P=.009), role emotional (P=.03), and general health perception (P=.03)—with the role physical showing the greatest magnitude of mean change (75.45 in the 3M group vs 53.04 in the R group). Notably, PCS was impaired to a greater extent than MCS in patients in the R group and showed a greater magnitude of improvement after 3 months of treatment. These results could be explained by the fact that MCS can be largely changed in diseases with a direct effect on the central nervous system.²³

Our results also revealed that the dose of corticosteroid correlated to HRQOL of patients with pemphigus who recently received RTX therapy. Indeed, it is more likely that patients on lower-dose prednisolone have a higher QOL, especially on physical function and social function dimensions of SF-36. This finding is highly expectable by less severe disease due to RTX treatment and also lower potential dose-dependent adverse effects of long-term steroid therapy.

One of the most striking findings of this study was the correlation of location of lesions to QOL indices. We found that the mucocutaneous phenotype was significantly correlated to greater improvement in role emotional, role physical, and social functioning scores due to RTX treatment compared with cutaneous or mucosal types (P=.02, P=.025, and P=.017, respectively). Although mucosal involvement of the disease can be the most burdensome feature because of its large impact on essential activities such as eating and speaking, cutaneous lesions with unpleasant appearance and undesirable symptoms may have a similar impact on QOL. Therefore, having both mucosal and cutaneous lesions causes a worsened QOL and decreased treatment efficacy vs having only one area involved. This may explain the greater improvement in some QOL indices with RTX treatment.

Limitations—Given the cross-sectional design of this study in which patients were observed at a single time point during their treatment course, it is not possible to establish a clear cause-effect relationship between variables. Moreover, we did not evaluate the impact of RTX or prednisolone adverse effects on QOL. Therefore, further prospective studies with longer treatment durations may help to validate our findings. In addition, MCDs for DLQI and SF-36 in pemphigus need to be determined and validated in future studies.

CONCLUSION

The results of our study demonstrated that patients with pemphigus may benefit from taking RTX, not only in terms of clinical improvement of their disease measured by objective indices such as PDAI and anti-DSG1 and anti-DSG3 values but also in several domains that are important to patients, including physical and mental health status (SF-36), HRQOL (DLQI), and overall disease severity (PGA). Rituximab administration in patients with pemphigus can lead to rapid and significant improvement in HRQOL as well as patient- and physician-assessed measures. Its favorable safety profile along with its impact on patients’ daily lives and mental health makes RTX a suitable treatment option for patients with pemphigus. Moreover, we recommend taking QOL indices into account while evaluating the efficacy of new medications to improve our insight into the patient experience and provide better patient adherence to treatment, which is an important issue for optimal control of chronic disorders.

Pemphigus is a group of autoimmune blistering diseases characterized by the development of painful and flaccid blisters on the skin and/or mucous membranes. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are 2 major subtypes and can be distinguished by the location of blister formation or the specificity of autoantibodies directed against different desmogleins.^1,2 Although rare, pemphigus is considered a serious and life-threatening condition with a great impact on quality of life (QOL) due to disease symptoms (eg, painful lesions, physical appearance of skin lesions) as well as treatment complications (eg, adverse drug effects, cost of treatment).^3-6 Moreover, the physical and psychological effects can lead to marked functional morbidity and work-related disability during patients’ productive years.⁷ Therefore, affected individuals usually have a remarkably compromised health-related quality of life (HRQOL).⁸ Effective treatments may considerably improve the QOL of patients with pemphigus.⁶

Despite the available treatment options, finding the best regimen for pemphigus remains a challenge. Corticosteroids are assumed to be the main treatment, though they have considerable side effects.^9,10 Adjuvant therapies are used to suppress or modulate immune responses, leading to remission with the least possible need for corticosteroids. Finding an optimal steroid-sparing agent has been the aim of research, and biologic agents seem to be the best option.⁸ Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown great promise in several studies of its clinical efficacy and has become a first-line treatment in new guidelines.^11-14 Rituximab treatment has been associated with notable improvement in physician-assessed outcome measures with a favorable safety profile in patients with pemphigus.^11-15 However, it is important to assess response to treatment from a patient’s perspective through the use of outcome-assessment measures that encompass patient-reported outcomes to reflect the complete patient experience and establish the overall impact of RTX as well as its likelihood of acceptance by patients with pemphigus.

In our study, we compared clinical outcomes and HRQOL through the use of disease-specific measures as well as comprehensive generic health status measures among patients with PV and PF who received RTX treatment 3 months earlier and those who received RTX in the last 2 weeks. The clinical relevance of the patient-reported outcomes is discussed.

MATERIALS AND METHODS

Study Design

We conducted a single-center cross-sectional study of 96 patients with pemphigus aged 18 to 65 years of either sex who were willing to participate in this study. Patients with a confirmed diagnosis of PV or PF who received RTX 3 months earlier or in the last 2 weeks were enrolled in the study. Patients were identified using Dermatry.ir, an archiving software that contains patients’ medical data. Exclusion criteria included lack of sufficient knowledge of the concepts of the questionnaires as well as age younger than 16 years. The study was conducted from October 2019 to April 2020 by the Autoimmune Bullous Disease Research Center at Razi Hospital in Tehran, Iran, which is the main dermatology-specific center and teaching hospital of Iran. The study protocol was approved by the relevant ethics committee.

Patients were categorized into 2 groups: (1) those who received RTX 3 months earlier (3M group); and (2) those who received RTX in the last 2 weeks (R group).

After an explanation of the study to participants, informed written consent was signed by each patient, and their personal data (eg, age, sex, education, marital status, smoking status), as well as clinical data (eg, type of pemphigus, duration of disease, site of onset, prednisolone dosage, presence of Nikolsky sign, anti-DSG1 and anti-DSG3 values, Pemphigus Disease Area Index [PDAI] score, RTX treatment protocol); any known comorbidities such as hypertension, diabetes mellitus, or morbid obesity; and any chronic pulmonary, cardiac, endocrinologic, renal, or hepatic condition, were collected and recorded in a predefined Case Record.

Patient-Reported Outcome Measures

The effect of RTX on QOL in patients with pemphigus was assessed using 2 HRQOL instruments: (1) a general health status indicator, the 36-Item Short Form Survey (SF-36), and (2) a validated, Persian version of a dermatology-specific questionnaire, Dermatology Life Quality Index (DLQI). The questionnaires were completed by each patient or by an assistant if needed.

The SF-36 is a widely used 36-item questionnaire measuring functional health and well-being across 8 domains—mental health, pain, physical function, role emotional, role physical, social functioning, vitality, and general health perception—with scores for each ranging from 0 to 100. The physical component scores (PCSs) and mental component scores (MCSs) were derived from these 8 subscales, each ranging from 0 to 400, with higher scores indicating better health status.⁶

The DLQI, one of the most frequently used QOL measures in dermatology, contains 10 questions, each referring to the prior week and classified in the following 6 subscales: symptoms and feelings, daily activities, leisure, personal relationships, work and school, and treatment.¹⁶ The total score ranges from 0 (no impact) to 30 (very high impact), with a higher score indicating a lower QOL (eTable 1). The minimal clinically important difference (MCD) for the DLQI was considered to be 2- to 5-point changes in prior studies.^17,18 In this study, we used an MCD of a 5-point change or more between study groups.

Moreover, the patient general assessment (PGA) of disease severity was identified using a 3-point scale (1=mild, 2=moderate, 3=severe).

Statistical Analysis

Data were analyzed using SPSS Statistics version 23. P≤.05 was considered significant. Mean and SD were calculated for descriptive data. The t test, Fisher exact test, analysis of variance, multiple regression analysis, and logistic regression analysis were used to identify the relationship between variables.

RESULTS

Patient Characteristics

A total of 96 patients were enrolled in this study. The mean (SD) age of participants was 41.42 (15.1) years (range, 18–58 years). Of 96 patients whose data were included, 55 (57.29%) patients had received RTX 3 months earlier (3M group) and 41 (42.71%) received RTX in the last 2 weeks (R group). A summary of study patient characteristics in each group is provided in eTable 2. There was no significant difference between the 2 groups in terms of age, sex, type of pemphigus, marital status, education, positive Nikolsky sign, smoking status, existence of comorbidities, site of lesions, and RTX treatment protocol. However, a significant difference was found for duration of disease (P=.0124) and mean prednisolone dosage (P=.001) as well as severity of disease measured by PDAI score (P=.003) and anti-DSG1 (P=.003) and anti-DSG3 (P=.021) values.

Patient-Reported Outcomes

Physical and mental component scores are summarized in eTable 3. Generally, SF-36 scores were improved with RTX treatment in all dimensions except for mental health, though these differences were not statistically significant, with the greatest mean improvement in the role physical index (75.45 in the 3M group vs 53.04 in the R group; P=.009). Mean SF-36 PCS and MCS scores were higher in the 3M group vs the R group, though the difference in MCS score did not reach the level of significance (eTable 3).

Mean DLQI scores in the R and 3M groups were 12.31 and 6.96, respectively, indicating a considerable burden on HRQOL in both groups. However, a statistically significant difference between these values was seen that also was clinically meaningful, indicating a significant improvement of QOL in patients receiving RTX 3 months earlier (P=.005)(eTable 3).

The PGA scores indicated that patients in the 3M group were significantly more likely to report less severe disease vs the R group (P=.008)(eTable 3).

Multivariate Analysis—Effect of the patient characteristics and some disease features on indices of QOL was evaluated using the multiple linear regression model. eTable 4 shows the P values of those analyses.

COMMENT

Pemphigus is a chronic disabling disease with notable QOL impairment due to disease burden as well as the need for long-term use of immunosuppressive agents during the disease course. To study the effect of RTX on QOL of patients with pemphigus, we compared 2 sets of patients. Prior studies have shown that clinically significant effects of RTX take 4 to 12 weeks to appear.^19,20 Therefore, we selected patients who received RTX 3 months earlier to measure their HRQOL indices and compare them with patients who had received RTX in the last 2 weeks as a control group to investigate the effect of RTX intrinsically, as this was the focus of this study.

In our study, one of the research tools was the DLQI. Healthy patients typically have an average score of 0.5.²¹ The mean DLQI score of the patients in R group was 12.31, which was similar to prior analysis⁸ and reflects a substantial burden of disease comparable to atopic dermatitis and psoriasis.^21,22 In patients in the 3M group, the mean DLQI score was lower than the R group (6.96 vs 12.31), indicating a significant (P=.005) and clinically meaningful improvement in QOL of patients due to the dramatic therapeutic effect of RTX. However, this score indicated a moderate effect on HRQOL, even in the context of clinical improvement due to RTX treatment, which may reflect that the short duration of treatment in the 3M group was a limitation of this study. Although the 12-week treatment duration was comparable with other studies^19,20 and major differences in objective measures of treatment efficacy were found in PDAI as well as anti-DSG1 and anti-DSG3 values, longer treatment duration may be needed for a more comprehensive assessment of the benefit of RTX on HRQOL indices in patients with pemphigus.

Based on results of the SF-36 questionnaire, PCS and MCS scores were not substantially impaired in the R group considering the fact that a mean score of 50 has been articulated as a normative value for all scales.²³ These data demonstrated the importance of using a dermatologic-specific instrument such as the DLQI instead of a general questionnaire to assess QOL in patients with pemphigus. However, better indices were reported with RTX treatment in the 3 SF-36 domains—role physical (P=.009), role emotional (P=.03), and general health perception (P=.03)—with the role physical showing the greatest magnitude of mean change (75.45 in the 3M group vs 53.04 in the R group). Notably, PCS was impaired to a greater extent than MCS in patients in the R group and showed a greater magnitude of improvement after 3 months of treatment. These results could be explained by the fact that MCS can be largely changed in diseases with a direct effect on the central nervous system.²³

Our results also revealed that the dose of corticosteroid correlated to HRQOL of patients with pemphigus who recently received RTX therapy. Indeed, it is more likely that patients on lower-dose prednisolone have a higher QOL, especially on physical function and social function dimensions of SF-36. This finding is highly expectable by less severe disease due to RTX treatment and also lower potential dose-dependent adverse effects of long-term steroid therapy.

One of the most striking findings of this study was the correlation of location of lesions to QOL indices. We found that the mucocutaneous phenotype was significantly correlated to greater improvement in role emotional, role physical, and social functioning scores due to RTX treatment compared with cutaneous or mucosal types (P=.02, P=.025, and P=.017, respectively). Although mucosal involvement of the disease can be the most burdensome feature because of its large impact on essential activities such as eating and speaking, cutaneous lesions with unpleasant appearance and undesirable symptoms may have a similar impact on QOL. Therefore, having both mucosal and cutaneous lesions causes a worsened QOL and decreased treatment efficacy vs having only one area involved. This may explain the greater improvement in some QOL indices with RTX treatment.

Limitations—Given the cross-sectional design of this study in which patients were observed at a single time point during their treatment course, it is not possible to establish a clear cause-effect relationship between variables. Moreover, we did not evaluate the impact of RTX or prednisolone adverse effects on QOL. Therefore, further prospective studies with longer treatment durations may help to validate our findings. In addition, MCDs for DLQI and SF-36 in pemphigus need to be determined and validated in future studies.

CONCLUSION

The results of our study demonstrated that patients with pemphigus may benefit from taking RTX, not only in terms of clinical improvement of their disease measured by objective indices such as PDAI and anti-DSG1 and anti-DSG3 values but also in several domains that are important to patients, including physical and mental health status (SF-36), HRQOL (DLQI), and overall disease severity (PGA). Rituximab administration in patients with pemphigus can lead to rapid and significant improvement in HRQOL as well as patient- and physician-assessed measures. Its favorable safety profile along with its impact on patients’ daily lives and mental health makes RTX a suitable treatment option for patients with pemphigus. Moreover, we recommend taking QOL indices into account while evaluating the efficacy of new medications to improve our insight into the patient experience and provide better patient adherence to treatment, which is an important issue for optimal control of chronic disorders.

Pemphigus is a group of autoimmune blistering diseases characterized by the development of painful and flaccid blisters on the skin and/or mucous membranes. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are 2 major subtypes and can be distinguished by the location of blister formation or the specificity of autoantibodies directed against different desmogleins.^1,2 Although rare, pemphigus is considered a serious and life-threatening condition with a great impact on quality of life (QOL) due to disease symptoms (eg, painful lesions, physical appearance of skin lesions) as well as treatment complications (eg, adverse drug effects, cost of treatment).^3-6 Moreover, the physical and psychological effects can lead to marked functional morbidity and work-related disability during patients’ productive years.⁷ Therefore, affected individuals usually have a remarkably compromised health-related quality of life (HRQOL).⁸ Effective treatments may considerably improve the QOL of patients with pemphigus.⁶

Despite the available treatment options, finding the best regimen for pemphigus remains a challenge. Corticosteroids are assumed to be the main treatment, though they have considerable side effects.^9,10 Adjuvant therapies are used to suppress or modulate immune responses, leading to remission with the least possible need for corticosteroids. Finding an optimal steroid-sparing agent has been the aim of research, and biologic agents seem to be the best option.⁸ Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown great promise in several studies of its clinical efficacy and has become a first-line treatment in new guidelines.^11-14 Rituximab treatment has been associated with notable improvement in physician-assessed outcome measures with a favorable safety profile in patients with pemphigus.^11-15 However, it is important to assess response to treatment from a patient’s perspective through the use of outcome-assessment measures that encompass patient-reported outcomes to reflect the complete patient experience and establish the overall impact of RTX as well as its likelihood of acceptance by patients with pemphigus.

In our study, we compared clinical outcomes and HRQOL through the use of disease-specific measures as well as comprehensive generic health status measures among patients with PV and PF who received RTX treatment 3 months earlier and those who received RTX in the last 2 weeks. The clinical relevance of the patient-reported outcomes is discussed.

MATERIALS AND METHODS

Study Design

We conducted a single-center cross-sectional study of 96 patients with pemphigus aged 18 to 65 years of either sex who were willing to participate in this study. Patients with a confirmed diagnosis of PV or PF who received RTX 3 months earlier or in the last 2 weeks were enrolled in the study. Patients were identified using Dermatry.ir, an archiving software that contains patients’ medical data. Exclusion criteria included lack of sufficient knowledge of the concepts of the questionnaires as well as age younger than 16 years. The study was conducted from October 2019 to April 2020 by the Autoimmune Bullous Disease Research Center at Razi Hospital in Tehran, Iran, which is the main dermatology-specific center and teaching hospital of Iran. The study protocol was approved by the relevant ethics committee.

Patients were categorized into 2 groups: (1) those who received RTX 3 months earlier (3M group); and (2) those who received RTX in the last 2 weeks (R group).

After an explanation of the study to participants, informed written consent was signed by each patient, and their personal data (eg, age, sex, education, marital status, smoking status), as well as clinical data (eg, type of pemphigus, duration of disease, site of onset, prednisolone dosage, presence of Nikolsky sign, anti-DSG1 and anti-DSG3 values, Pemphigus Disease Area Index [PDAI] score, RTX treatment protocol); any known comorbidities such as hypertension, diabetes mellitus, or morbid obesity; and any chronic pulmonary, cardiac, endocrinologic, renal, or hepatic condition, were collected and recorded in a predefined Case Record.

Patient-Reported Outcome Measures

The effect of RTX on QOL in patients with pemphigus was assessed using 2 HRQOL instruments: (1) a general health status indicator, the 36-Item Short Form Survey (SF-36), and (2) a validated, Persian version of a dermatology-specific questionnaire, Dermatology Life Quality Index (DLQI). The questionnaires were completed by each patient or by an assistant if needed.

The SF-36 is a widely used 36-item questionnaire measuring functional health and well-being across 8 domains—mental health, pain, physical function, role emotional, role physical, social functioning, vitality, and general health perception—with scores for each ranging from 0 to 100. The physical component scores (PCSs) and mental component scores (MCSs) were derived from these 8 subscales, each ranging from 0 to 400, with higher scores indicating better health status.⁶

The DLQI, one of the most frequently used QOL measures in dermatology, contains 10 questions, each referring to the prior week and classified in the following 6 subscales: symptoms and feelings, daily activities, leisure, personal relationships, work and school, and treatment.¹⁶ The total score ranges from 0 (no impact) to 30 (very high impact), with a higher score indicating a lower QOL (eTable 1). The minimal clinically important difference (MCD) for the DLQI was considered to be 2- to 5-point changes in prior studies.^17,18 In this study, we used an MCD of a 5-point change or more between study groups.

Moreover, the patient general assessment (PGA) of disease severity was identified using a 3-point scale (1=mild, 2=moderate, 3=severe).

Statistical Analysis

Data were analyzed using SPSS Statistics version 23. P≤.05 was considered significant. Mean and SD were calculated for descriptive data. The t test, Fisher exact test, analysis of variance, multiple regression analysis, and logistic regression analysis were used to identify the relationship between variables.

RESULTS

Patient Characteristics

A total of 96 patients were enrolled in this study. The mean (SD) age of participants was 41.42 (15.1) years (range, 18–58 years). Of 96 patients whose data were included, 55 (57.29%) patients had received RTX 3 months earlier (3M group) and 41 (42.71%) received RTX in the last 2 weeks (R group). A summary of study patient characteristics in each group is provided in eTable 2. There was no significant difference between the 2 groups in terms of age, sex, type of pemphigus, marital status, education, positive Nikolsky sign, smoking status, existence of comorbidities, site of lesions, and RTX treatment protocol. However, a significant difference was found for duration of disease (P=.0124) and mean prednisolone dosage (P=.001) as well as severity of disease measured by PDAI score (P=.003) and anti-DSG1 (P=.003) and anti-DSG3 (P=.021) values.

Patient-Reported Outcomes

Physical and mental component scores are summarized in eTable 3. Generally, SF-36 scores were improved with RTX treatment in all dimensions except for mental health, though these differences were not statistically significant, with the greatest mean improvement in the role physical index (75.45 in the 3M group vs 53.04 in the R group; P=.009). Mean SF-36 PCS and MCS scores were higher in the 3M group vs the R group, though the difference in MCS score did not reach the level of significance (eTable 3).

Mean DLQI scores in the R and 3M groups were 12.31 and 6.96, respectively, indicating a considerable burden on HRQOL in both groups. However, a statistically significant difference between these values was seen that also was clinically meaningful, indicating a significant improvement of QOL in patients receiving RTX 3 months earlier (P=.005)(eTable 3).

The PGA scores indicated that patients in the 3M group were significantly more likely to report less severe disease vs the R group (P=.008)(eTable 3).

Multivariate Analysis—Effect of the patient characteristics and some disease features on indices of QOL was evaluated using the multiple linear regression model. eTable 4 shows the P values of those analyses.

COMMENT

Pemphigus is a chronic disabling disease with notable QOL impairment due to disease burden as well as the need for long-term use of immunosuppressive agents during the disease course. To study the effect of RTX on QOL of patients with pemphigus, we compared 2 sets of patients. Prior studies have shown that clinically significant effects of RTX take 4 to 12 weeks to appear.^19,20 Therefore, we selected patients who received RTX 3 months earlier to measure their HRQOL indices and compare them with patients who had received RTX in the last 2 weeks as a control group to investigate the effect of RTX intrinsically, as this was the focus of this study.

In our study, one of the research tools was the DLQI. Healthy patients typically have an average score of 0.5.²¹ The mean DLQI score of the patients in R group was 12.31, which was similar to prior analysis⁸ and reflects a substantial burden of disease comparable to atopic dermatitis and psoriasis.^21,22 In patients in the 3M group, the mean DLQI score was lower than the R group (6.96 vs 12.31), indicating a significant (P=.005) and clinically meaningful improvement in QOL of patients due to the dramatic therapeutic effect of RTX. However, this score indicated a moderate effect on HRQOL, even in the context of clinical improvement due to RTX treatment, which may reflect that the short duration of treatment in the 3M group was a limitation of this study. Although the 12-week treatment duration was comparable with other studies^19,20 and major differences in objective measures of treatment efficacy were found in PDAI as well as anti-DSG1 and anti-DSG3 values, longer treatment duration may be needed for a more comprehensive assessment of the benefit of RTX on HRQOL indices in patients with pemphigus.

Based on results of the SF-36 questionnaire, PCS and MCS scores were not substantially impaired in the R group considering the fact that a mean score of 50 has been articulated as a normative value for all scales.²³ These data demonstrated the importance of using a dermatologic-specific instrument such as the DLQI instead of a general questionnaire to assess QOL in patients with pemphigus. However, better indices were reported with RTX treatment in the 3 SF-36 domains—role physical (P=.009), role emotional (P=.03), and general health perception (P=.03)—with the role physical showing the greatest magnitude of mean change (75.45 in the 3M group vs 53.04 in the R group). Notably, PCS was impaired to a greater extent than MCS in patients in the R group and showed a greater magnitude of improvement after 3 months of treatment. These results could be explained by the fact that MCS can be largely changed in diseases with a direct effect on the central nervous system.²³

Our results also revealed that the dose of corticosteroid correlated to HRQOL of patients with pemphigus who recently received RTX therapy. Indeed, it is more likely that patients on lower-dose prednisolone have a higher QOL, especially on physical function and social function dimensions of SF-36. This finding is highly expectable by less severe disease due to RTX treatment and also lower potential dose-dependent adverse effects of long-term steroid therapy.

One of the most striking findings of this study was the correlation of location of lesions to QOL indices. We found that the mucocutaneous phenotype was significantly correlated to greater improvement in role emotional, role physical, and social functioning scores due to RTX treatment compared with cutaneous or mucosal types (P=.02, P=.025, and P=.017, respectively). Although mucosal involvement of the disease can be the most burdensome feature because of its large impact on essential activities such as eating and speaking, cutaneous lesions with unpleasant appearance and undesirable symptoms may have a similar impact on QOL. Therefore, having both mucosal and cutaneous lesions causes a worsened QOL and decreased treatment efficacy vs having only one area involved. This may explain the greater improvement in some QOL indices with RTX treatment.

Limitations—Given the cross-sectional design of this study in which patients were observed at a single time point during their treatment course, it is not possible to establish a clear cause-effect relationship between variables. Moreover, we did not evaluate the impact of RTX or prednisolone adverse effects on QOL. Therefore, further prospective studies with longer treatment durations may help to validate our findings. In addition, MCDs for DLQI and SF-36 in pemphigus need to be determined and validated in future studies.

CONCLUSION

The results of our study demonstrated that patients with pemphigus may benefit from taking RTX, not only in terms of clinical improvement of their disease measured by objective indices such as PDAI and anti-DSG1 and anti-DSG3 values but also in several domains that are important to patients, including physical and mental health status (SF-36), HRQOL (DLQI), and overall disease severity (PGA). Rituximab administration in patients with pemphigus can lead to rapid and significant improvement in HRQOL as well as patient- and physician-assessed measures. Its favorable safety profile along with its impact on patients’ daily lives and mental health makes RTX a suitable treatment option for patients with pemphigus. Moreover, we recommend taking QOL indices into account while evaluating the efficacy of new medications to improve our insight into the patient experience and provide better patient adherence to treatment, which is an important issue for optimal control of chronic disorders.